Biology subjects

Kreisel, T.

Publications and source records attributed to Kreisel, T..

8 recordsLinked to original sources

bioRxiv2026

The nucleus of the lateral olfactory tract is required for learning odor-guided food avoidance

Foraging animals must continually evaluate whether potential food sources are safe to consume. Such decisions rely on both innate preferences and learned associations formed through prior experience. Consumption of a food followed by malaise or sickness leads to avoidance of that food, reflecting learned associations between sensory cues that identify a food and its negative post-ingestive consequences. Although this form of learning has been studied extensively using taste cues, taste signals arise only after oral contact, at which point exposure to potential toxins has already occurred. Olfactory cues, in contrast, provide information about potential food sources prior to consumption, yet how odors acquire aversive value remains unclear. Here, using targeted chemogenetic perturbations, we identify the nucleus of the lateral olfactory tract (NLOT), which has direct bidirectional connectivity to olfactory regions and the basolateral amygdala, as a critical circuit element for odor-aversion learning. We find that the NLOT is required for conditioned odor aversion but is dispensable for other odor-guided behaviors and for fear conditioning driven by a non-olfactory cue. Our findings identify a selective role for the NLOT in linking olfactory cues to learned aversive outcomes, that supports odor-guided behavioral decisions. Significance statementAnimals rely on smell to evaluate food safety before consuming it, yet the brain circuits that link odor cues to learned aversive outcomes remain poorly understood. Here we identify the nucleus of the lateral olfactory tract (NLOT), a largely unstudied region at the interface between olfactory and limbic circuits, as a critical and selective node for conditioned odor aversion learning. Chemogenetic perturbations of the NLOT disrupted both the acquisition and expression of odor-malaise associations, while leaving odor detection, odor discrimination, and non-olfactory fear learning intact -- revealing a previously unrecognized specialization within olfactory-amygdala circuits that supports odor-guided decisions about food safety.

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bioRxiv2025

Astrocytic Activation Completely Corrects Memory Performancein an Alzheimer's Disease Model

Neural and glial dysfunction are thought to underlie memory impairments in Alzheimers disease (AD). Conversely, astrocytes are known to play a central role in the healthy brain, and their activation has been shown to enhance memory. To test whether activation of astrocytes can correct memory deficits associated with AD, we expressed hM3Dq in CA1 astrocytes of 7 months old 5XFAD AD model mice, enabling astrocytic chemogenetic Gq pathway activation, following exposure to CNO. We report that astrocytic activation results in complete memory correction, and even memory improvement of AD model mice beyond that of untreated WT levels. We went further to discover the mechanisms underlying this memory improvement in AD mice: First, using 2-photon imaging and electrophysiology, we observed increased neuronal activity (displayed as elevated cFos expression and amplified awake Ca2+ events) as well as augmented in-vivo long term plasticity following astrocytic activation. Subsequently, we observed increased astrocytic endocytosis of A{beta} plaques. Finally, we report that the beneficial effects of astrocytic activation remained stable for an entire year, and persisted beyond the window of astrocytic Gq activation. Our findings that astrocytes correct memory impairments in an AD model could have important clinical implications towards treating this disease.

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bioRxiv2025

Enhanced reward coding and condition-independent dynamics in optogenetically identified corticostriatal neurons in monkeys

The basal ganglia are considered to be the site where cortical sensorimotor and dopaminergic reward information interact to potentiate and select actions. This had led to the assumption that cortical inputs to the basal ganglia encode sensorimotor states rather than reward or choice signals. We tested this hypothesis by studying the coding properties of neurons in the frontal eye field of monkeys that were optogenetically identified as being connected to the basal ganglia. We found that neurons already contained information about expected rewards and selected actions. Further, the reward and condition-independent modulations were stronger in connected neurons than in other neurons in the same area. These findings indicate that reward, choice, and sensorimotor information are integrated already in the inputs to the basal ganglia, implying that the basal ganglia play a role in manipulating rather than generating reward and choice signals.

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bioRxiv2023

Astrocytes Control Recent and Remote Memory Strength by Affecting the Recruitment of the CA1->ACC Projection to Engrams

Recent and remote memories are encoded throughout the brain in Engrams: cell ensembles formed during acquisition, and upon their reactivation, a specific memory can be recalled. The maturation of engrams from recent to remote time points involves the recruitment of CA1 neurons projecting to the anterior cingulate cortex (CA1[->]ACC). Various modifications to CA1 astrocytes, to the Gq- or Gi-GPCR pathways, during memory acquisition were shown to affect recent and remote recall in seemingly contradictory ways. To address the inconsistency, we applied transgenic approaches for ensemble identification, CLARITY, retro-AAV virus for circuit mapping, and chemogenetics in astrocytes for functional investigation. We manipulated the activity of either Gq- or Gi-pathways in CA1 astrocytes during memory acquisition and tagged cFos+ engram cells and CA1[->]ACC cells during recent and remote recall in the same animals. The behavioral results were coupled with changes in the recruitment of CA1[->]ACC projection cells to the engram, demonstrated by the number of CA1[->]ACC projecting cells in the engram as well as the number of axons projecting from the CA1 engram toward the ACC: Gq pathway activation in astrocytes caused enhancement of recent recall alone and was accompanied by earlier recruitment of CA1[->]ACC projecting cells to the engram. In contrast, when activating the Gi pathway in astrocytes during acquisition, only remote recall was impaired, and CA1[->]ACC projecting cells were not recruited during remote memory. Finally, we provide a simple working model, hypothesizing that astrocytes control behavioral performance by targeting the CA1[->]ACC projection. Specifically, that Gq- and Gi-pathway activation affect memory differently, but do so by modulating the same mechanism. These findings illuminate the importance of astrocytes in the acquisition of fear memory and their implications on recent and remote recall.

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bioRxiv2022

Engram Stability and Maturation During Systems Consolidation Underlies Remote Memory

Remote memories play an important role in how we perceive the world and are rooted in ensembles in the CA1 and ACC, however the evolution of these components during systems consolidation has not yet been comprehensively addressed. By applying transgenic approaches for ensemble identification, CLARITY, retro-AAV and rabies virus for circuit mapping, and chemogenetics for functional interrogation, we addressed the dynamics of CA1-ACC ensembles and their connectivity as well as the contribution of astrocytes to the process. We found that the CA1 engrams remain stable between recent and remote recall, and, the inhibition of the engram for recent recall during remote recall functionally impairs memory. We also found that the new cells in the remote recall engram in the CA1 are not added randomly, but differ according to their connections: First, the anterograde CA1 [->] ACC engram cell projection grows larger. Second, in the retrograde projections, the ACC reduces input to CA1 engram cells, while input from the entorhinal cortex and paraventricular nucleus of the thalamus increases. Finally, we found that activating CA1 astrocytes during acquisition improves recent but not remote recall, and that CA1 [->] ACC projecting cells are recruited earlier when the astrocytes are stimulated. Our results shine fresh light on systems consolidation by providing a deeper understanding of engram stability and maturation in the transition from recent to remote memory.

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bioRxiv2021

Hippocampal Astrocytes Encode Reward Location

Astrocytic calcium dynamics have been implicated in the encoding of sensory information, and modulating them has been shown to impact behavior. However, real-time calcium activity of astrocytes in the hippocampus of awake mice has never been investigated. We used 2-photon microscopy to chronically image CA1 astrocytes as mice ran in familiar or novel virtual environments and obtained water rewards. We found that astrocytes exhibit persistent ramping activity towards the reward location in a familiar environment, but not in a novel one. Using linear decoders, we could precisely predict the location of the mouse in a familiar environment from astrocyte activity alone. We could not do the same in the novel environment, suggesting astrocyte spatial activity is experience dependent. This is the first indication that astrocytes can encode location in spatial contexts, thereby extending their known computational capabilities, and their role in cognitive functions.

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bioRxiv2020

Features Of Hippocampal Astrocytic Domains And Their Spatial Relation To Excitatory And Inhibitory Neurons

The mounting evidence for the involvement of astrocytes in neuronal circuits function and behavior stands in stark contrast to the lack of detailed anatomical description of these cells and the neurons in their domains. To fill this void, we imaged >30,000 astrocytes in cleared hippocampi, and employed converging genetic, histological and computational tools to determine the elaborate structure, distribution and neuronal content of astrocytic domains. First, we characterized the spatial distribution of >19,000 astrocytes across CA1 lamina, and analyzed the detailed morphology of thousands of reconstructed domains. We then determined the excitatory content of CA1 astrocytes, averaging above 13 pyramidal neurons per domain and increasing towards CA1 midline. Finally, we discovered that somatostatin neurons are found in close proximity to astrocytes, compared to parvalbumin and VIP inhibitory neurons. This resource expands our understanding of fundamental hippocampal design principles, and provides the first quantitative foundation for neuron-astrocyte interactions in this region.

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bioRxiv2019

Astrocytes Contribute to Remote Memory Formation by Modulating Hippocampal-Cortical Communication During Learning

The consolidation and retrieval of remote memories depend on the coordinated activity of the hippocampus and frontal cortices. However, the exact time at which these regions are recruited to support memory and the interactions between them are still debated. Astrocytes can sense and modify neuronal activity with great precision, but their role in cognitive function has not been extensively explored. To investigate the role of astrocytes in remote memory we expressed the Gi-coupled receptor hM4Di in CA1 astrocytes, allowing their manipulation by a designer drug. We discovered that astrocytic modulation during learning resulted in a specific impairment in remote, but not recent, memory recall, accompanied by decreased neuronal activity in the anterior cingulate cortex (ACC) during retrieval. We revealed a massive recruitment of ACC-projecting neurons in CA1 during memory acquisition, accompanied by activation of ACC neurons. Astrocytic Gi activation disrupted CA3 to CA1 communication in-vivo, and reduced the downstream response in the ACC. This same manipulation in behaving mice induced a projection-specific inhibition of ACC-projecting CA1 neurons during learning, consequently preventing the recruitment of the ACC. Our findings suggest that the foundation of remote memory is established in the ACC during acquisition, engaging a distinct process from the one supporting consolidation of recent memory. Furthermore, the mechanism underlying remote memory involves projection-specific functions of astrocytes in regulating neuronal activity.

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